Accelerated enhanced recovery after colon cancer surgery with discharge within one day after surgery: a systematic review

Background Recent studies have demonstrated that accelerated enhanced recovery after colorectal surgery is feasible for specific patient populations. The accelerated enhanced recovery protocols (ERP) tend to vary, and the majority of studies included a small study population. This hampers defining the optimal protocol and establishing the potential benefits. This systematic review aimed to determine the effect of accelerated ERPs with intended discharge within one day after surgery. Methods PubMed (MEDLINE), Embase, Cochrane and Web of Science databases were searched using the following search terms: colon cancer, colon surgery, accelerated recovery, fast track recovery, enhanced recovery after surgery. Clinical trials published between January 2005 – February 2023, written in English or Dutch comparing accelerated ERPs to Enhanced Recovery After Surgery (ERAS) care for adult patients undergoing elective laparoscopic or robotic surgery for colon cancer were eligible for inclusion. Results Thirteen studies, including one RCT were included. Accelerated ERPs after colorectal surgery was possible as LOS was shorter; 14 h to 3.4 days, and complication rate varied from 0–35.7% and readmission rate was 0–17% in the accelerated ERP groups. Risk of bias was serious or critical in most of the included studies. Conclusions Accelerated ERPs may not yet be considered the new standard of care as the current data is heterogenous, and data on important outcome measures is scarce. Nonetheless, the decreased LOS suggests that accelerated recovery is possible for selected patients. In addition, the complication and readmission rates were comparable to ERAS care, suggesting that accelerated recovery could be safe. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-023-11803-4.


Background
Since the introduction of the Enhanced Recovery After Surgery (ERAS) protocol by Kehlet et al. [1], there is increasing interest in recovery after surgery.The evidence-based interventions of the ERAS protocol have shown to reduce perioperative stress, maintain postoperative physiological functioning and accelerate recovery after surgery [2].When combined with laparoscopic surgery, ERAS care effectuated a reduced Length Of hospital Stay (LOS) and morbidity, faster recovery with no increase in readmissions, and cost reduction compared with traditional care [1,[3][4][5][6][7][8].
The positive effects of ERAS piqued clinicians' interest in the possibility of further accelerating recovery by improving perioperative care.Recent studies have shown that an accelerated enhanced recovery protocol (ERP) is feasible for specific patients without compromising patients' safety with discharge of all patients on the day of surgery to three days after colorectal surgery [9][10][11][12][13][14][15][16].These results were obtained from studies that have explored ERPs with an optimized preoperative, perioperative, and postoperative protocol.The patient selection and accelerated ERP protocol differed between studies and included adjusted preoperative analgesia, Transversus Abdominis Plane (TAP) block during surgery, modified postoperative care with home visits by a domiciliary nurse or monitoring using a smartphone application [11,12,17].The accelerated ERPs could potentially result in adaptation of perioperative care guidelines for colorectal cancer surgery.However, based on the current data, the optimal patient selection and protocol of an accelerated ERP is difficult to determine.Moreover, there is a certain ambiguity on what benefits this protocol could offer and which patients are suitable for accelerated recovery.
The aim of this systematic review was to determine the effect of accelerated ERPs with intended hospital discharge within one day after surgery compared to standard ERAS care on LOS, surgical outcomes, quality of life (QoL) and cost-effectiveness for patients undergoing elective surgery for colon cancer.

Methods
This systematic review was prospectively registered in the PROSPERO database (CRD42023406341).The guidelines described in the Cochrane Handbook for Systematic Reviews of Interventions, Version 6.3, 2022 for the conduct of the review and the Preferred Reporting Items for Systematic Reviews and Meta-analysis of Individual Participant Data (PRISMA) guidelines for preparing the manuscript were followed [18,19].

Literature search
A systematic literature search in four key healthcare databases was conducted.PubMed (MEDLINE), Embase, Cochrane and Web of Science databases were searched from inception until February 10th, 2023.The following search terms were used: colon cancer, colon surgery, accelerated recovery, fast track recovery, enhanced recovery after surgery.For the literature search, there was no restriction on publication type or date.In addition, we searched trial registries (PROSPERO and ClinicalTrials.gov) for unpublished trials.Also, the reference lists of key records were assessed for additional relevant studies.

Eligibility criteria
Clinical trials published from the first of January 2005, written in English or Dutch comparing an accelerated ERP to ERAS care for patients undergoing elective surgery for colon cancer were eligible for inclusion.This time restriction was selected since the first ERAS guideline was published in 2005, therefore it would be very unlikely that any relevant trials would be found prior to this year [1].Studies were not restricted on study type but had to include at least a study population of 10 patients, with an age ≥ 18 years.To create a homogenous patient population, studies had to involve patients undergoing elective laparoscopic or robot-assisted surgical resections for colon cancer.Studies that included only benign or rectal surgery were excluded,

Study selection
The results of the literature search were collected and deduplicated in the Rayyan software [20].All articles were first screened for relevance on title and abstract independently by two reviewers MS and AG.Full text articles were retained if they met the eligibility criteria described above.After retrieving and examining the full text of all potentially relevant articles, both reviewers indicated independently if the study should be included.Any discrepancies were double-checked and resolved by discussion with other members of the review team (JS and TL).When there were multiple reports featuring the same dataset, the publication with the longest duration of follow-up was included to diminish overlap and to include the largest patient population.If the study selection would yield less than 500 patients included in the accelerated ERP, also non-comparative ERP studies would be described.

ERPs
We defined accelerated ERPs as accelerated enhanced recovery protocols with intended discharge within one day after surgery.Same day discharge (SDD) protocols were defined as protocols with intended discharge < 24 h after surgery without overnight hospital stay.Protocols that included overnight stay, were classified as ≤ 24 h stay protocols.Given the variation in protocol adaptations of ERPs, no restrictions on ERP elements were defined.Since the implementation of ERAS protocols varies between hospitals, we have set the limit on at least 7 ERAS items used in the control (ERAS) group to create a consistency in the provided ERAS care.This is in line with the Cochrane review of Spanjersberg et al. [3].

Outcomes
The following data were extracted systematically from the included papers: author, publication year, study design, type of ERP and ERAS protocol, number of participants, patients' characteristics, surgical data, i.e., indication for surgery and type of resection, and clinical outcomes.The primary outcome of this study was primary LOS (defined as number of days admitted after surgery).Secondary outcomes were total LOS (defined as number of days admitted after surgery and potential readmission days within 90 days after surgery), overall complications within 90 days after surgery (graded by the Clavien Dindo classification [21]), readmissions within 90 days after surgery, Quality of Life (QoL) and cost-effectiveness.If available, QoL was determined using disease specific PROMs [22].Costs included only intramural hospital costs and were reported in the monetary unit of the study.

Assessment of risk of bias in included studies
The potential source of bias of the included randomized trials was assessed using the RoB 2-tool [23], for nonrandomized studies the ROBIN-I tool was used [24].The robvis-tool was used to create risk-of-bias plots [25].Each study was assessed using this method by reviewers MS and AG independently.Discrepancies were solved by consensus discussion with a third reviewer JS, if necessary.
The outcomes of all studies were reported using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system [18].

Statistical analysis
We extracted all data use from the original studies.To quantify the statistical heterogeneity in the studies, the I 2 value was used.Only if studies were sufficiently clinically, methodologically, and statistically homogenous, the data were pooled in a meta-analysis.In case of considerable heterogeneity (> 75%), descriptive quantitative analysis and qualitative analysis would be performed and outcomes between included studies described [18].

Selected studies
This systematic search identified 28,342 articles.All references from the four search databases were imported into Rayyan bibliographic software.The literature search and selection processes are shown in Fig. 1.After removing the duplicates, a total of 17,797 references were screened and assessed for eligibility based on title and abstract.Of these, 144 full-text articles were assessed for eligibility of which 5 studies met the inclusion criteria.Due to the limited number of included patients, non-comparative, and retrospective studies describing accelerated ERPs were also included.No additional studies were included based on reference check.In total 13 studies were included [9,11,12,17,[26][27][28][29][30][31][32][33][34].The baseline characteristics of the included studies, patient demographics and outcomes are shown in Tables 1 and 2.

Risk of bias
The methodological quality is presented in risk of bias (RoB) summaries (Figs.2,3,4,5).Blinding of participants and personnel was not possible due to the nature of the intervention.Eight studies had a serious or critical risk of bias [9, 12, 26-28, 30, 32, 33], which was due to confounding, selection bias, bias in measurement or bias in the selection of reported results.Five cohort studies had moderate risk of bias [11,17,29,31,34].Overall, the methodological quality of the included studies ranged from moderate to low.Due to the heterogeneity of studies, GRADE criteria could not be applied.

ERP protocol
Upon analysing the ERP groups, studies applied different modifications to or put extra emphasis on specific ERAS elements during the pre-operative, peri-and postoperative phases.An overview of the pre-, peri-, postoperative and post discharge protocol adjustments of the accelerated ERPs is listed in Table 3.

Heterogeneity
The studies varied clinically (e.g., patient population, type of ERP) and methodologically (e.g., cohort, randomized trial).Different outcome measures were reported in various ways across studies.Therefore, a meta-analysis was not feasible.A quantitative analysis was performed for the results of LOS, postoperative complications, readmissions, and patient satisfaction.

Patients' characteristics
Age, gender, ASA, indication for surgery (benign/ malignant), and surgical procedures are displayed in Tables 4 and 5.

Cost-effectiveness/costs
None of the studies included provided data on costeffectiveness of the ERP compared to standard care.

Discussion
This systematic review evaluated the effect of accelerated ERPs with intended discharge within one day after  complication and readmission rates of the accelerated ERP group were similar to patients treated according to the current ERAS care.Upon implementing accelerated ERP, more robust research is needed to establish the optimal protocol and its effects.
Previous reviews have implied the potential of accelerated ERPs but stated that the body of evidence was relatively low due to heterogeneity of studies [36,37].New studies have been published recently [11,17,26,28], therefore it was deemed important to conduct a new systematic review.A robust body of evidence in favour of accelerated ERP could reduce clinicians' restraint to implement accelerated ERPs after colorectal surgery.Currently, there remains fear of increased readmissions, potential delays in treating complications and confusion due to the variety of adapted care elements.
A few studies reported primary LOS [9,11,12,17,29,31,32], which varied widely (14 h [11]-3.4days [29]).The LOS was remarkably lower among patients treated according to accelerated discharge protocol compared with the median LOS of 4 days of the entire Dutch patient population in as reported by the Dutch Colorectal Audit [38].It is important to bear in mind that this major reduction in LOS could be attributed to the selection of a relatively healthy patient population, to the strict discharge criteria, to the approach and urgency of surgery or to the extensive follow-up.Therefore, this finding cannot be extrapolated to all patients.Nonetheless, these protocols may also reduce LOS for patient populations other than those studied.There is a potential bias from the fact that a primary goal of the accelerated ERP's was to reduce LOS; this could have affected outcome parameter in comparative studies.
The readmission rate of this review was higher than described in previous reviews [36,37].The discrepancy could be partly explained by the larger number of patients included in this review [11,17,26,28,31,32,34].Furthermore, the majority of the additionally included studies were prospective studies [11,17,26,28,31,32], used broader inclusion criteria [28,31] or had an older study population [26].Two comparative studies reported a considerably higher readmission rate in the accelerated ERP population [26,32].The authors of both studies considered this difference in readmission rate to be unrelated to the intervention based on the reasons for readmission, being i.e. bowel obstruction due to a port-site hernia, rectal blood loss or pneumonia.Despite the higher readmission rate, the rate of serious complications was comparable [26].As these complications were detected in a timely fashion, potential delay in diagnosis and treatment was low.
This review shows comparable readmission rates compared with the international readmission rate of 5.5-16% [39][40][41].This supports the idea that accelerated ERPs do not increase readmission.
Accelerated recovery can only be considered to be successful if patient safety is guaranteed.The few studies that compared complication rates reported higher but not statistically significant differences in rates of minor complications in the group with accelerated recovery.The rates of anastomotic leakage were comparable between the two arms and mortality rates were low in both groups, suggesting that the accelerated ERP could be safe.
Even though the increase in minor complication will hardly affect patients' safety or readmission rate, it could effectuate increase in emergency room visits or lower patient satisfaction.Few studies described emergency department (ED) visits [12,17,27,29,32], Two studies reported a slight increase in ED visits in the accelerated ERP group [12,26,32].The complication rate of this review is higher than reported in previous reviews [36,37].The larger number of prospective studies could be a possible explanation for the higher rate of complications as well as differences in patient characteristics, indications for surgery and types of surgery [11,17,26,[30][31][32].
In general, complications occur in approximately 30% of patients after oncological colorectal resections [42,43].As this review includes mostly relatively healthy and young patients, it is to be expected that most reported complication rates in this review were lower than in the general surgical population.The generalizability of these results is limited since the way complications were reported across studies was not constant between studies, nor were definitions of complications or the complication rates.As method for follow-up was not defined in all studies, it remains unclear whether all complications were scored.
The included studies all used slightly different inclusion criteria, but most of the included subjects had a limited medical record.Thus, little data exists to guarantee safety of implementing an accelerated ERAS protocol in a population with extended co-morbidity or higher age.
A minority of the studies provided information about long term outcome parameters such as oncological survival or quality of life but available literature showed high patient satisfaction and quality of life [26,32].The economic effects of the intervention have not been investigated yet.The number of studies performing costanalysis is limited, but it is plausible that this reduction in LOS results in lower healthcare costs as long as it does not increase the use of healthcare after discharge.

Strengths and limitations
This study has some limitations.First, the studies were heterogeneous in terms of the accelerated ERP protocols, length of follow-up and patient population, indications for surgery and types of surgical procedures.Several studies included patients undergoing colon and rectum cancer surgery, while these surgical procedures and the postoperative course differ [12,17,27,29,30,32,34,38]. The difference between protocols may be due to the fact that exact knowledge on separate effects of modified or emphasized ERAS-elements is lacking.It has been shown that the strength of ERAS is the sum of its elements [3].Nonetheless, due to the heterogeneity, studies are hardly comparable or applicable to a broader patient population.The ERAS protocol of the control cohort has not been described in detail; therefore, it is difficult to determine what ERASelements were incorporated into the standard care.
Available data provided little information regarding QoL, long-term outcomes, protocol adherence or implementation.Despite today's emphasis on reducing the rising cost of health care, none of the studies described cost-effectiveness.Some accelerated ERPs included extensive home monitoring; the financial impact would be worth noting.Overall risk of bias was moderate to critical.Only one RCT was included, all other studies were cohort studies.Methodological quality was low.Moreover, some studies included patients in the early discharge cohort based on postoperative measures.Therefore, the measured effects might be under-or overestimated.A strength of this review is the extensive literature search and updated overview of the current protocols and outcomes of accelerated ERPs.Further large clinical trial with a well-defined intervention and control group, which take clearly defined complications with a follow-up of at least 30 days, QoL, cost-effectiveness, protocol adherence, and its implementation into account, will need to be undertaken.These studies could initiate the development of a uniform accelerated ERP.

Conclusion
Based on current evidence, this systematic review has shown, that the accelerated ERP may not yet be considered the new standard of care as the current data is heterogenous, and important outcome measures are lacking.However, since the results are promising in selected patients, there is need to conduct large, randomized trials with strict separation between accelerated ERP and ERAS protocols.

Fig. 1
Fig. 1 PRISMA flow diagram of the literature search and selection procedure

Table 1
Characteristics included comparative studies, patient demographics, ERP versus ERAS, and outcomes 1 I Intervention (ERP) 2 C Control (ERAS) 3 MIS Minimally Invasive Surgery 4 CD Clavien Dindo 5 AL anastomotic leakage 6 SSI surgical site infection 7 SDD Same-Day Discharge 8 NI not investigated 9 AF atrial fibrillation

Table 2
Characteristics included non-comparative studies, patient demographics, ERP versus ERAS, and outcomes 1 NI Not investigated 2 AL Anastomotic Leakage 3 SSI surgical site infection 4 SDD Same-Day Discharge (discharge on day of surgery) 5 TAP Transversus Abdominis Plane 6 CD Clavien Dindo classification

Table 3
Overview of specific ERAS targets in accelerated ERPs

Table 4
Patients' characteristics comparative studies

1 /C 2 ) ASA (I 1 /C 2 ) Indication for surgery Benign: malignant (I 1 /C 2 ) Types of surgery performed (I 1 /C 2 )
colorectal surgery.Thirteen studies were included in this review, one RCT was identified.Due to heterogeneity, no meta-analysis could be performed.Risk of bias was serious or critical in the majority of included studies, level of evidence was considered low.The results of this systematic review demonstrate that accelerated ERPs after colorectal surgery are applicable for a selected patient population as LOS was shorter.The

Table 5
Patients' characteristics non-comparative studies